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To the Editor:

I read with interest the letter by Saravana and Rai in reaction to the editorial Anemia of Chronic Disease in Patients with RA. The question raised by Saravana and Rai is very important, related to which test is the best method for detection of iron-deficiency erythropoiesis (IDE) in patients with RA. Next to the question, which test could also predict the eventual effect on iron supplementation in restoring the anemia. In the past different methods were proposed and investigated: the measurement of the percentage of hypochromic red blood cells, content of hemoglobulin in reticulocytes, soluble transferrin receptor, ferritin levels, and zinc protoporphyrin (ZPP) levels.

Presently, serum ferritin levels are the most common test in daily practice. The remark by Saravana and Rai that serum ferritin level is not a reliable indicator of iron deficiency, because it behaves as an acute phase reactant, is partly correct. However, by defining a cutoff < 50 µg/l we were able to show that this value correlated with the results obtained in bone marrow smears (no stainable iron), but also with the effect of iron supplementation. In this way the use of serum ferritin levels in RA was validated. In a recent study¹ ZPP, the soluble transferrin receptor, and the hemoglobulin content of reticulocytes were investigated as a diagnostic and prognostic parameter in RA patients with anemia of chronic disease. In our study the value of serum ferritin was confirmed, and no additional benefit of the other measures for predicting or monitoring IDE was shown. To claim that a test can be used for the diagnosis of IDE, the test has to be validated in the defined disease. For example, in patients with renal disease no significant correlation could be demonstrated between ZPP levels and IDE^2-4. In these studies it was concluded that ZPP could not be used to predict the erythropoietic response to iron supplementation.

The same holds true for serum ferritin levels; however, in these studies a cutoff value of < 100 µg/l was defined for IDE. But it should be stressed that patients undergoing dialysis often showed raised serum ferritin levels, which is not explained. Still, a weak correlation could be demonstrated in another study⁵. Therefore, it should be stressed that for every disease the defined measure has to be validated. In this way the ZPP levels are not investigated in a prospective way in RA patients with anemia of chronic disease and IDE.

ANTONIUS J.G. SWAAK, MD, Department of Rheumatology, Ruwaard van Putten Ziekenhuis, Rotterdam, The Netherlands. E-mail: swaak@rpz.nl

REFERENCES

1. Arndt U, Kaltwasser JP, Gottschalk R, Hoelzer D, Moller B. Correction of iron-deficient erythropoiesis in the treatment of anemia of chronic disease with recombinant human erythropoietin. Ann Hematol 2005;84:159-66. EPub 2004 November 234. [MEDLINE]

2. Garrett S, Worwood M. Zinc protoporphyrin and iron-deficient erythropoiesis. Acta Haematol 1994;91:21-5. [MEDLINE]

3. Baldus M, Walter H, Thies K, et al. Transferrin receptor assay and zinc protoporphyrin as markers of iron-deficient erythropoiesis in end-stage renal disease patients. Clin Nephrol 1998;49:186-92. [MEDLINE]

4. Braun J, Hammerschmidt M, Schreiber M, Heidler R, Horl WH. Is zinc protoporphyrin an indicator of iron-deficient erythropoiesis in maintenance haemodialysis patients? Nephrol Dial Transplant 1996;11:492-7. [MEDLINE]

5. Braun J, Lindner K, Schreiber M, Heidler RA, Horl WH. Percentage of hypochromic red blood cells as predictor of erythropoietic and iron response after i.v. iron supplementation in maintenance haemodialysis patients. Nephrol Dial Transplant 1997;12:1173-81. [MEDLINE]